Functional profiling of OSP-specific and other antibodies during shigella infection

志贺氏菌感染期间 OSP 特异性抗体和其他抗体的功能分析

• 批准号: 10687224
• 负责人: Edward T. Ryan
• 金额: $ 76.19万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-22 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10687224
• 关键词: Acute; Address; Adult; American; Antibodies; Antibody Affinity; Antibody Response; Antibody titer measurement; Antigens; Area; Attenuated; Bangladesh; Binding; Biological Assay; Biophysics; Cessation of life; Child; Complement; Complement Activation; Conjugate Vaccines; Data; Enzyme-Linked Immunosorbent Assay; Evaluation; Fc Receptor; Future; General Hospitals; Genetic Complementation Test; Goals; Household; Human; Immune response; Immune system; Immunity; Immunoglobulin Constant Region; Immunologics; Infection; Innate Immune System; Invaded; Knowledge; Massachusetts; Mediating; Modeling; Morbidity - disease rate; Mucins; NK Cell Activation; O Antigens; Organism; Pattern; Phagocytes; Phagocytosis; Plasmids; Play; Process; Public Health; Research; Research Design; Research Institute; Research Personnel; Resource-limited setting; Resources; Role; Sampling; Sampling Studies; Shigella; Shigella Infections; Shigella Vaccines; Shigella sonnei; Specificity; System; Universities; Vaccinated; Vaccination; Vaccines; Validation; Virulence Factors; Work; arm; bactericide; diarrheal disease; glycosylation; international center; monocyte; mortality; neutrophil; pathogen; response; vaccine candidate; vaccine development; vaccine evaluation; vaccine trial; volunteer

PROJECT SUMMARY/ABSTRACT Shigella infection is a leading cause of diarrheal illness in young children in resource-limited settings, and results in tens of thousands of deaths each year. Protection against shigellosis is associated with antibodies targeting O-specific polysaccharide (OSP), but immune responses against other antigens have also been noted to correlate with protection. Functional attributes of anti-shigella antibodies have also been noted to correlate with protection, including complement activation and ability to induce host cell phagocytic activity. Despite this, a shigella OSP-conjugate vaccine failed to protect young children in a field trial, despite providing protection in older children and adults. We propose that such issues may reflect differences not only in antibody magnitude (titer) following vaccination, but also differences in antibody functional effector attributes, including Fc interactions with the innate immune system. Such differences have been noted to correlate with protection against a range of infectious pathogens. To address this, we propose to define antibody functional and biophysical attributes associated with protection against shigella infection, including in young children, using a household contact study design approach in an informal settlement area in Dhaka, Bangladesh. We propose to complement this analysis with data from North American vaccine and Controlled Human Infection Models (CHIMs) and related studies. We anticipate that we will identify a profile of antibody attributes that correlates with protection against shigellosis, that this knowledge will critically guide vaccine development and evaluation efforts, and that this knowledge will focus future mechanistic studies.

项目总结/文摘